Project Title: Electroretinogram: A New Human Biomarker for Smoking Cessation Treatment Project Summary: In this application for a K23 Mentored Patient Oriented Research Career Development Award, Dr. Sean Luo proposes a comprehensive plan for developing into an independent researcher to develop biomarkers in substance use disorders, and in particular, tobacco use disorder. Specifically, this proposal will focus on developing a new human biomarker, electroretinogram, for dopamine release. Tobacco smoking continues to be a major public health challenge. Several lines of evidence suggest that dopamine release deficit is involved in the development and maintenance of nicotine dependence. We hypothesize that those smokers who do not have a deficit in dopamine release will more likely respond to behavioral treatments for smoking cessation, and in particular, financial incentives contingent on abstinence (Contingency Management). Previous pilot data suggest that flash blue cone electroretinogram (ERG), which records electrical signals from the retina in response to light, is a clinically accessible correlate to dopamine release in the brain. We propose an ERG-based biomarker, and a pilot clinical trial to apply this biomarker to personalize smoking cessation treatment. This clinically tractable biomarker of central dopamine release may have a large number of future applications in the diagnosis and treatment of other mental illnesses and substance use disorders. While pursuing this line of research with the expertise of his mentors (Dr. Edward Nunes and Dr. Frances Levin) and preceptors (Drs. Diana Martinez, Stephen Tsang, Alan Budney and Jill Williams), Dr. Luo will concurrently engage in an individualized training program so as to develop in the following important areas: (1) retinal physiology and biomarker development (2) retinal data analytic methods (3) clinical research methods (4) behavioral and pharmacological treatment of tobacco use disorder (5) grant writing and administration.